The Non-Classical Secretion of Thioredoxin from Breast Cancer Cells
Final rept. 1 Jun 2001-31 May 2004
BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA
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Thioredoxin is a small protein with a catalytic site for redox reactions that is involved in several physiologic and pathophysiologic processes in humans. A ubiquitous cytosolic protein, thioredoxin also is secreted by some types of cells including cells derived from leukemia, lung, colon, and breast cancers. Extracellular thioredoxin acts as an autocrine growth factor and can potentiate the action of other cytokines on these tumor cell lines. The novel pathway by which thioredoxin is secreted has not been elucidated. Our aims were to identify the amino acid sequence within thioredoxin that directs its secretion from cells, and to identify the cellular gene products that secrete thioredoxin from breast cancer cells. We characterized the non-classical secretion of thioredoxin from several cell types. We also discovered that this route of export can be used to dispose of unfolded proteins.
- Medicine and Medical Research